ArticleOncogene2012
Role of MUC4-NIDO domain in the MUC4-mediated metastasis of pancreatic cancer cells.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Potential of Fibulin2 as a therapeutic target against cancer and as a diagnostic marker (Review).International journal of oncology · 2025Review
- Lymphadenectomy in upper tract urothelial carcinoma: Clinical insights and controversies (Review).Oncology reports · 2025Review
- Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues.Molecular oncology · 2024Article
- Trace elements in pancreatic cancer.Cancer medicine · 2024Review
- Lung Inflammatory Phenotype in Mice Deficient in Fibulin-2 and ADAMTS-12.International journal of molecular sciences · 2024Article
- Lymph Node Dissection in Upper Tract Urothelial Carcinoma: Current Status and Future Perspectives.Current oncology reports · 2023Review
- Fibulin-2 Facilitates Malignant Progression of Hepatocellular Carcinoma.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Targeted O-glycoproteomics for the development of diagnostic markers for advanced colorectal cancer.Frontiers in oncology · 2023Article
- Nidogen1-enriched extracellular vesicles accelerate angiogenesis and bone regeneration by targeting Myosin-10 to regulate endothelial cell adhesion.Bioactive materials · 2022Article
- Mucin Expression and Splicing Determine Novel Subtypes and Patient Mortality in Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- The role of membrane mucin MUC4 in breast cancer metastasis.Endocrine-related cancer · 2021Review
- Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2021Article
- Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.Biomolecules · 2021Review
- MUC4 enhances gemcitabine resistance and malignant behaviour in pancreatic cancer cells expressing cancer-associated short O-glycans.Cancer letters · 2021Article
- Fibulin-2 expression associates with vascular invasion and patient survival in breast cancer.PloS one · 2021Article
- Unraveling mucin domains in cancer and metastasis: when protectors become predators.Cancer metastasis reviews · 2020Review
- Correlation of Fibulin-2 expression with proliferation, migration and invasion of breast cancer cells.Oncology letters · 2020Article
- Roles of Fibulin-2 in Carcinogenesis.Medical science monitor : international medical journal of experimental and clinical research · 2020Review
- Prognostic Utility of FBLN2 Expression in Patients With Urothelial Carcinoma.Frontiers in oncology · 2020Article
- The expression level of fibulin-2 in the circulating RNA (ctRNA) of epithelial tumor cells of peripheral blood and tumor tissue of patients with metastatic lung cancer.Molecular biology reports · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
MUC4 is a large transmembrane type I glycoprotein that is overexpressed in pancreatic cancer (PC) and has been shown to be associated with its progression and metastasis. However, the exact cellular and molecular mechanism(s) through which MUC4 promotes metastasis of PC cells has been sparsely studied. Here we showed that the nidogen-like (NIDO) domain of MUC4, which is similar to the G1-domain present in the nidogen or entactin (an extracellular matrix protein), contributes to the protein-protein interaction property of MUC4. By this interaction, MUC4 promotes breaching of basement membrane (BM) integrity, and spreading of cancer cells. These observations are corroborated with the data from our study using an engineered MUC4 protein without the NIDO domain, which was ectopically expressed in the MiaPaCa PC cells, lacking endogenous MUC4 and nidogen protein. The in vitro studies demonstrated an enhanced invasiveness of MiaPaCa cells expressing MUC4 (MiaPaCa-MUC4) compared with vector-transfected cells (MiaPaCa-Vec; P=0.003) or cells expressing MUC4 without the NIDO domain (MiaPaCa-MUC4-NIDO(Δ); P=0.03). However, the absence of NIDO-domain has no significant role on cell growth and motility (P=0.93). In the in vivo studies, all the mice orthotopically implanted with MiPaCa-MUC4 cells developed metastasis to the liver as compared with MiaPaCa-Vec or the MiaPaCa-MUC4-NIDO(Δ) group, hence, supporting our in vitro observations. Additionally, a reduced binding (P=0.0004) of MiaPaCa-MUC4-NIDO(Δ) cells to the fibulin-2 coated plates compared with MiaPaCa-MUC4 cells indicated a possible interaction between the MUC4-NIDO domain and fibulin-2, a nidogen-interacting protein. Furthermore, in PC tissue samples, MUC4 colocalized with the fibulin-2 present in the BM. Altogether, our findings demonstrate that the MUC4-NIDO domain significantly contributes to the MUC4-mediated metastasis of PC cells. This may be partly due to the interaction between the MUC4-NIDO domain and fibulin-2.
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